The most prominent feature of cortex is the arrangement
of neurons into layers with classical “neocortex” identified as
having six layers. Because these layers differ in thickness, cell
type, and cell density from one part of the cortex to another,
these “laminar” differences have been used to subdivide the
cortex into different regions (e.g. Brodmann, 1909; Vogt and
Vogt, 1919; von Economo and Koskinas, 1925; Von Bonin
and Bailey, 1947; Petrides and Pandya, 1994). It has also been
noted that different cortical regions display a “vertical” organization
of neurons grouped into columnar arrangements that
take two forms: macrocolumns, approximately 0.4–0.5 mm
in diameter (Mountcastle, 1957; Calvin, 1995), and microcolumns
or minicolumns approximately 30 microns in diameter
(Jones, 2000).

Macrocolumns were first identified functionally by
Mountcastle (1957), who described groups of neurons in somatosensory
cortex that respond to light touch alternating
with laterally adjacent groups that respond to joint and/or
muscle stimulation. These groups form a mosaic with a
periodicity of about 0.5 mm. Similarly, Hubel and Wiesel
(1963, 1969, 1977) using both monkeys and cats discovered
alternating macrocolumns of neurons in the visual cortex
that respond preferentially to the right or to the left eye.
These “ocular dominance columns” have a spacing of about
0.4 mm. In addition, they discovered within the ocular dominance
columns smaller micro- or minicolumns of neurons
that respond preferentially to lines in a particular orientation.

Once these physiological minicolumns were recognized,
it was noted that vertically organized columns of this approximate
size are visible in many cortical areas under low
magnification and are composed of perhaps 100 neurons
stretching from layer V through layer II. To prove that the
physiological and morphologically defined minicolumns or
microcolumns are identical to the physiologically defined
minicolumn would require directly measuring the response
of a majority of the neurons in a single histologically identified
microcolumn, but this has yet to be done. Nevertheless,
current data on the microcolumn indicate that the neurons
within the microcolumn receive common inputs, have
common outputs, are interconnected, and may well constitute
a fundamental computational unit of the cerebral cortex
(e.g. Szentagothai, 1975; Swindale, 1990; Purves et al.,
1992; Saleem et al., 1993; Van Hoesen and Solodkin, 1993;
Buxhoeveden et al., 1996; Mountcastle, 1997; Buxhoeveden
and Casanova, 2002a,b; Mountcastle, 2003). These microcolumns
vary in spacing across the cortex and species,
but are about 30 microns apart in human visual cortex (Calvin,
1995).

The microcolumn has recently been shown to be disrupted
in a number of different conditions including Alzheimer’s
Disease (AD) and Lewy Body dementia (LBD) (Buldyrev
et al., 2000), autism (Casanova et al., 2002a), dyslexia
(Casanova et al., 2002b), and schizophrenia (Buxhoeveden
et al., 2000b). Interestingly, in normal aging monkeys where
cortical neurons are largely preserved (e.g. Peters et al., 1998)
there is evidence of age-related functional disruption of orientation
selectivity in the visual cortex of aged monkeys
(Schmolesky et al., 2000; Leventhal et al., 2003). In these
studies, Leventhal and colleagues reported a loss of two functional
properties of microcolumns—orientation and direction
selectivity. Moreover, they demonstrated that administration
of GABA agonists restored these functions. Since the small
GABAergic interneurons are important components of the
microcolumn, this suggests that there may well be a disruption
of at least this or a related component of the microcolumn
in normal aging.